Preterm birth is the leading cause of neonatal morbidity arid mortality. The rate of preterm birth in the United States has increased progressively from 9% to 12% over the past two decades.Recent studies haveshown that prophylactic administration of progesterone (intramuscular or intravaginal) may prevent preterm birth in women with history of spontenous preterm labor. This lead to recommendations by the American College of Obstetricians and Gynecologists, March of Dimes and National Institute of Child Health and Development that supplemental progesterone be offered to all womenwith previous history of spontaneous preterm birth. However, it is still unclear which high risk woman would truly benefit from this treatment in a general clinical setting and whether socio-cultural and racial differencesplay a role in patients' response to supplemental progesterone. In addition, the provider and patients acceptance of such recommendation is also in question. The primary aim of this proposal is determine whether the availability of IM 17-P to women with history of spontaneous preterm birth who are seen in the context of routine obstetrical care will result in a significant reduction (33%) in preterm birth. The secondary aims are 1.) To gain a better understanding of the clinical use of 17-P by identifying those who may be eligible for its administration for the prevention of preterm birth and evaluate the barriers to patient's acceptance and adherence including socio-cultural and racial differences, 2.) To develop knowledge regarding potential novel solutions to ensure acceptance and adherence to the use of progesterone supplementation in the reduction of preterm birth, and 3.) To perform assay by design based genotyping of all informative and non-redundant single nucleotide polymorphisms (SNPs) of the genes related to the pathways of the activity of the human progesterone gene (both maternal and fetal cord blood or buccal smear) to determine if there are differences in the human progesterone receptor gene that explain responders and non-responders of 17-P treatment.